Harr 5.7 Enzymes and Cardiac Markers
34. A patient has a plasma CK-MB of 14 μg/L at admission and a total CK of 170 IU/L. Serum myoglobin is 130 μg/L and TnI is 1.6 μg/L. Three hours later, the TnI is 3.0 μg/L. Which statement best describes this situation? A. This patient has had an AMI and further testing is unnecessary B. A second CK-MB and myoglobin test should have been performed at 3 hours postadmission to confirm AMI C. These results are consistent with skeletal muscle damage associated with a crush injury that elevated the CK-MB D. Further testing 6-12 hours postadmission is required to establish a diagnosis of AMI
A (Results on admission indicate strongly that the patient has suffered an MI. The 3-hour TnI confirms this and rules out the possibility of a sample collection or transcription error for the admission sample. Repeat testing of other cardiac markers at 3 hours was not necessary because admission results were significantly increased for all three markers. Skeletal muscle damage or crush injury does not cause an increase in cardiac TnI.)
26. In a nonmyocardial as opposed to a myocardial cause of an increased serum or plasma CK-MB, which would be expected? A. An increase in CK-MB that is persistent B. An increase in the percent CK-MB as well as concentration C. The presence of increased TnI D. A more modest increase in total CK than CK-MB
A (Plasma CK-MB becomes abnormal 4 hours postinfarction, peaks in 16-20 hours, and usually returns to normal within 48 hours. In some noncardiac causes of elevated plasma CK-MB such as muscular dystrophy, there is a persistent elevation of both total CK and CK-MB. TnI and TnT are cardiac-specific markers. They become elevated slightly before CK-MB when a CK-MB URL of 4 μg/L is used, remain elevated for 7-10 days following an AMI, and are not increased in muscular dystrophy, malignant hyperthermia, or crush injuries that are associated with an increase in the concentration of CK-MB. Absolute CK-MB increases are evaluated cautiously, when CK-MB is less than 2.5% of total enzyme because noncardiac sources may be responsible.)
6. Which of the following statements is true? A. Apoenzyme + prosthetic group = holoenzyme B. A coenzyme is an inorganic molecule required for activity C. Cofactors are as tightly bound to the enzyme as prosthetic groups D. All enzymes have optimal activity at pH 7.00
A (A coenzyme is an organic molecule required for full enzyme activity. A prosthetic group is a coenzyme that is tightly bound to the apoenzyme and is required for activity. Cofactors are inorganic atoms or molecules needed for full catalytic activity. Pyridoxyl- 5´-phosphate is a prosthetic group for ALT and AST. Consequently, patients with low levels of pyridoxal- 5´-phosphate (P-5´-P) (vitamin B6 deficiency) may have reduced transaminase activity in vitro. Enzymes can have diverse pH (and temperature) optimas.)
2. Which of the following statements describes a nonkinetic enzyme assay? A. Initial absorbance is measured followed by a second reading after 5 minutes B. Absorbance is measured at 10-second intervals for 100 seconds C. Absorbance is monitored continuously for 1 minute using a chart recorder D. Reflectance is measured from a xenon source lamp pulsing at 60 Hz
A (A kinetic assay uses several evenly spaced absorbance measurements to calculate the change in absorbance per unit time. A constant change in absorbance per unit of time occurs only when the rate of the reaction is zero order (independent of substrate concentration). Enzyme activity is proportional to rate only under zero-order conditions.)
5. Which substrate concentration is needed to achieve zero-order conditions? A. Greater than 99 × Km B. [S] = Km C. Less than 10 × Km D. [S] = 0
A (A zero-order reaction rate is independent of substrate concentration because there is sufficient substrate to saturate the enzyme. V = Vmax × [S]/Km + [S] where V = velocity, Vmax = maximum velocity, [S] = substrate concentration, and Km = substrate concentration required to give 1/2 Vmax. If [S] >>> Km, then the Km can be ignored. V = Vmax × [S]/[S] = Vmax × [S]° or velocity approaches maximum and is independent of substrate concentration.)
16. In which type of liver disease would you expect the greatest elevation of LD? A. Toxic hepatitis B. Alcoholic hepatitis C. Cirrhosis D. Acute viral hepatitis
A (Liver disease produces an elevated LD-4 and LD-5. Levels may reach up to 10 times the URL in toxic hepatitis and in hepatoma. However, LD levels are lower in viral hepatitis (2-5 × URL), only slightly elevated in cirrhosis (2-3 × URL) and not significantly elevated in alcoholic liver disease.)
7. Which of the following statements about enzymatic reactions is true? A. NADH has absorbance maximas at 340 and 366 nm B. Enzyme concentration must be in excess to achieve zero-order kinetics C. Rate is proportional to substrate concentration in a zero-order reaction D. Accumulation of the product increases the reaction rate
A (Most enzymes are measured by monitoring the rate of absorbance change at 340 nm as NADH is produced or consumed. This rate will be proportional to enzyme activity when substrate is in excess. When the enzyme is present in excess, the initial reaction rate will be proportional to substrate concentration. This condition, called a first-order reaction, is needed when the enzyme is used as a reagent to measure a specific analyte.)
19. In the Oliver-Rosalki method for CK, adenosine monophosphate (AMP) is added to the substrate in order to: A. Inhibit adenylate kinase B. Block the oxidation of glutathione C. Increase the amount of ADP that is available D. Block the action of diadenosine pentaphosphate
A (Positive interference in the Oliver-Rosalki method can occur when adenylate kinase is present in the serum from hemolysis or damaged tissue. Adenylate kinase hydrolyzes ADP, forming AMP and ATP (2 ADP AK AMP + ATP). This reaction is inhibited by adding AMP and diadenosine pentaphosphate (Ap5A) to the substrate.)
17. Which of the following conditions will interfere with the measurement of LD? A. Slight hemolysis during sample collection B. Storage at 4°C for 3 days C. Storage at room temperature for 16 hours D. Use of plasma collected in heparin
A (RBCs are rich in LD-1 and LD-2, and even slight hemolysis will falsely elevate results. Hemolytic, megaloblastic, and pernicious anemias are associated with LD levels of 10-50 times the URL. LD is stable for 2 days at room temperature or 1 week at 4°C; however, freezing causes deterioration of LD-5. The activity of LD is inhibited by EDTA, which binds divalent cations; serum or heparinized plasma should be used.)
13. Which condition produces the highest elevation of serum lactate dehydrogenase? A. Pernicious anemia B. Myocardial infarction C. Acute hepatitis D. Muscular dystrophy
A (Serum LD levels are highest in pernicious anemia, reaching 10-50 times the upper reference limit (URL) as a result of intramedullary hemolysis. Moderate elevations (5-10 × URL) usually are seen in acute myocardial infarction, necrotic liver disease, and muscular dystrophy. Slight increases (2-3 × URL) are sometimes seen in obstructive liver disease.)
18. In the Oliver-Rosalki method, the reverse reaction is used to measure CK activity. The enzyme(s) used in the coupling reactions is (are): A. Hexokinase and G-6-PD B. Pyruvate kinase and LD C. Luciferase D. Adenylate kinase
A (The Oliver-Rosalki method for CK is based upon the formation of ATP from creatine phosphate. Hexokinase catalyzes the phosphorylation of glucose by ATP. This produces glucose-6-PO4 and adenosine diphosphate (ADP). The glucose-6-PO4 is oxidized to 6-phosphogluconate as NADP+ is reduced to NADPH. ATP + glucose Hexokinase ADP + glucose-6-PO4 glucose-6-PO4 + NADP+ G-6-PD 6-phosphogluconate + NADPH + H+ 19. A Positive interference in the Oliver-Rosalki method)
25. A patient's CK-MB is reported as 18 μg/L and the total CK as 560 IU/L. What is the CK relative index (CKI)? A. 0.10% B. 3.2% C. 10.0% D. 30.0%
B (The CKI is an expression of the percentage of the total CK that is attributed to CK-MB. CKI = CK-MB in μg/L × 100 Total CK in IU/L The reference range is 0%-2.5%. Values above 2.5% point to an increase in CK-MB from cardiac muscle.)
41. Which of the following statements about the aminotransferases (AST and ALT) is true? A. Isoenzymes of AST and ALT are not found in humans B. Both transfer an amino group to α-ketoglutarate C. Both require NADP+ as a coenzyme D. Both utilize four carbon amino acids as substrates
B (ALT catalyzes the transfer of an amino group from alanine, a three-carbon amino acid, to α-ketoglutarate (2-oxoglutarate), forming pyruvate. AST catalyzes the transfer of an amino group from aspartate (four carbons) to α-ketoglutarate, forming oxaloacetate. The reactions are highly reversible and regulate the flow of aspartate into the urea cycle. Both transaminases require P-5'-P as an intermediate amino acceptor (coenzyme). Cytoplasmic and mitochondrial isoenzymes are produced but are not differentiated in clinical practice.)
42. Select the products formed from the forward reaction of AST. A. Alanine and α-ketoglutarate B. Oxaloacetate and glutamate C. Aspartate and glutamine D. Glutamate and NADH
B (AST forms oxaloacetate and glutamate from aspartate and α-ketoglutarate (2-oxoglutarate). Both transaminases use α-ketoglutarate and glutamate as a common substrate and product pair. Both aspartate and alanine can be used to generate glutamate in the central nervous system, where it acts as a neurotransmitter.)
39. Which statement best describes the clinical utility of plasma homocysteine? A. Levels are directly related to the quantity of LDL cholesterol in plasma B. High plasma levels are associated with atherosclerosis and increased risk of thrombosis C. Persons who have an elevated plasma homocysteine will also have an increased plasma Lp(a) D. Plasma levels are increased only when there is an inborn error of amino acid metabolism
B (Homocysteine includes the monomeric amino acid as well as the dimers such as homocystine that contain homocysteine. Plasma levels are measured as an independent risk factor for coronary artery disease. High levels of homocysteine are toxic to vascular endothelium and promote inflammation and plaque formation. Plasma levels are independent of LDL and other cholesterol fractions and help explain why approximately 35% of people with first-time AMI have LDL cholesterol levels < 130 mg/dL.)
27. Which statement best describes the clinical utility of plasma or serum myoglobin? A. Levels greater than 100 μg/L are diagnostic of AMI B. Levels below 100 μg/L on admission and 2-4 hours postadmission help to exclude a diagnosis of AMI C. Myoglobin peaks after the cardiac troponins but is more sensitive D. The persistence of myoglobin > 110 μg/L for 3 days following chest pain favors a diagnosis of AMI
B (Myoglobin is a heme-containing pigment in both skeletal and cardiac muscle cells. The upper limit of normal is approximately 90 μg/L for males and 75 μg/L for females. The plasma myoglobin is a sensitive marker for AMI. Over 95% of affected persons have a value higher than the cutoff (typically >110 μg/L). However, specificity is approximately 75%-85% owing to skeletal muscle injury or renal insufficiency. For this reason, a plasma myoglobin below the cutoff on admission, and within the first 3 hours following chest pain helps to rule out AMI. A value above the cutoff must be confirmed using a cardiac specific assay such as TnI or TnT.)
32. Which of the following cardiac markers is consistently increased in persons who exhibit unstable angina? A. Troponin C B. Troponin T C. CK-MB D. Myoglobin
B (Persons with unstable angina (angina at rest) who have an elevated TnT or TnI are at eight times greater risk of having an MI within the next 6 months. This property is being used to identify short-term risk patients who should be considered for coronary angioplasty. The reference range for troponin is very low (0-0.03 ng/mL); persons with unstable angina usually have values between 0.04 and 0.1 ng/mL without clinical evidence of AMI. CK-MB and myoglobin have not been useful in identifying persons with unstable angina)
31. What is the recommended troponin T and I cutoff (upper limit of normal) for detecting myocardial infarction? A. The cutoff varies with the method of assay but should be no lower than 0.2 ng/mL B. The upper 99th percentile or lowest level that can be measured with 10% CV C. The concentration corresponding to the lowest level of calibrator used D. The highest value fitting under the area of the curve for the 95% confidence interval
B (The American College of Cardiology recommends the cutoff for an abnormal troponin test be set at the 99th percentile of the normal population, 0.013 ng/mL, or if the assay precision at this level is >10% then the cutoff should be the lowest value measurable with a CV of 10% (typically 0.03 ng/mL). An abnormal result (0.04 ng/mL or higher) in a patient with other evidence of ischemic changes indicates cardiac damage. This typically occurs when a pattern of increasing troponin concentration is seen over the first 6 hours after initial testing)
12. Which statement about methods for measuring LD is true? A. The formation of pyruvate from lactate (forward reaction) generates NAD+ B. The pyruvate-to-lactate reaction proceeds at about twice the rate as the forward reaction C. The lactate-to-pyruvate reaction is optimized at pH 7.4 D. The negative-rate reaction is preferred
B (Although the rate of the reverse reaction (P →L) is faster, the L →P reaction is more popular because it produces a positive rate (generates NADH), is not subject to product inhibition, and is highly linear. The pH optimum for the forward reaction is approximately 8.8.)
11. Which of the following enzymes is a transferase? A. ALP B. CK C. Amylase D. LD
B (Enzymes are identified by a numeric system called the EC (Enzyme Commission) number. The first number refers to the class of the enzyme. There are six classes; in order, these are oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Dehydrogenases are oxidoreductases, whereas kinases and transaminases are transferases. CK is EC number 2.7.3.2, which distinguishes it from other kinases.)
10. Which of the following enzymes is activated by calcium ions? A. CK B. Amylase C. ALP D. LD
B (Most enzymes require metals as activators or cofactors. CK and ALP require Mg+2 for full activity, and amylase requires Ca+2. Metals required for activity should be components of the substrate used for enzyme analysis. The substrate must also contain anions required (e.g., Cl- for amylase) and should not contain inhibiting cations or anions (e.g., Zn+2 and Mn+2 for CK).)
28. What is the typical time course for plasma myoglobin following an AMI? A. Abnormal before 1 hour; peaks within 3 hours; returns to normal in 8 hours B. Abnormal within 3 hours; peaks within 6 hours; returns to normal in 18 hours C. Abnormal within 2 hours; peaks within 12 hours; returns to normal in 36 hours D. Abnormal within 6 hours; peaks within 24 hours; returns to normal in 72 hours
C (After AMI, myoglobin usually rises above the cutoff within 1-2 hours, peaks within 8-12 hours and returns to normal within 36 hours. Typically, levels reach a peak concentration that is 10-fold the upper reference limit. Since myoglobin is the first marker to become abnormal after an AMI, it should be measured on admission and if negative, again 2 hours later. If both samples are below the cutoff, the probability of an AMI having occurred is low. If the myoglobin is above the cutoff, a cardiac specific marker such as TnI, or TnT must be performed at some point to confirm the diagnosis.)
38. Which statement best describes the clinical utility of B-type natriuretic peptide (BNP)? A. Abnormal levels may be caused by obstructive lung disease B. A positive test indicates prior myocardial damage caused by AMI that occurred within the last 3 months C. A normal test result (<100 pg/mL) helps rule out congestive heart failure in persons with symptoms associated with coronary insufficiency D. A level above 100 pg/mL is not significant if evidence of congestive heart failure is absent
C (B-type natriuretic peptide is a hormone produced by the ventricles in response to increased intracardiac blood volume and hydrostatic pressure. It is formed in the heart from a precursor peptide (preproBNP) by enzymatic hydrolysis, first forming proBNP followed by BNP and NT (N-terminal) proBNP which is not physiologically active. Both BNP and NT-proBNP are increased in persons with congestive heart failure (CHF). Levels are not increased in pulmonary obstruction, hypertension, edema associated with renal insufficiency, and other conditions that cause physical limitation and symptoms that overlap CHF. At a cutoff of <100 pg/mL the BNP test is effective in ruling out CHF. Diagnostic accuracy in distinguishing CHF from nonCHF ranges from 83%-95%. In addition, persons with ischemia who have an increased BNP are at greater risk for MI. The NTpro-BNP assay is similar in clinical value, and can be used for persons being treated with nesiritide, a recombinant form of BNP used to treat CHF.)
35. SITUATION: An EDTA sample for TnI assay gives a result of 0.04 ng/mL (reference range 0-0.03 ng/mL). The test is repeated 3 hours later on a new specimen and the result is 0.06 ng/mL. A third sample collected 6 hours later gives a result of 0.07 ng/mL. The EKG showed no evidence of ST segment elevation (STEMI). What is the most likely explanation? A. A false-positive result occurred due to matrix interference B. Heparin should have been used instead of EDTA, which causes false positives C. The patient has suffered cardiac injury D. The patient has had an ischemic episode without cardiac injury
C (EDTA is the additive of choice for troponin assays because it avoids microclots that can lead to false positive results when serum or heparinized plasma is used. Spurious false positives caused by matrix effects usually revert to normal when the test is repeated on a new sample. An AMI will cause the TnI to increase in subsequent tests. Results between 0.04-0.10 ng/mL are the result of cardiac injury, and indicate either AMI or an increased short-term risk of AMI.)
20. Which substance is used in the CK assay to activate the enzyme? A. Flavin adenine dinucleotide (FAD) B. Imidazole C. N-acetylcysteine D. Pyridoxyl-5´-phosphate Chemistry/Apply principles of
C (In addition to Mg+2, CK requires a thiol compound to reduce interchain disulfide bridges and bind heavy metals that inactivate the enzyme. N-acetylcysteine is an activator of CK used for this purpose in the IFCC recommended method. Pyridoxyl-5´-phosphate is a prosthetic group of AST and ALT. FAD is a prosthetic group of glucose oxidase. Imidazole is used to buffer the CK reagent.)
24. Which of the following statements regarding the clinical use of CK-MB (CK-2) is true? A. CK-MB becomes elevated before myoglobin after an AMI B. CK-MB levels are usually increased in cases of cardiac ischemia C. CK-MB is more specific than myoglobin D. An elevated CK-MB is always accompanied by an elevated total CK
C (Serum myoglobin becomes abnormal within 1-2 hours after an acute myocardial infarction (AMI) before troponin and CK-MB. CK-MB becomes abnormal shortly after troponin I (TnI) or troponin T (TnT) when a URL of 4 μg/L is used, and peaks at around the same time following AMI. However, cardiac troponins remain elevated significantly longer than CK-MB after AMI, are not increased in crush injuries. There is less than 5 μg/L CK-MB in the serum of healthy adults, while the total CK ranges from 10-110 U/L. Consequently, an abnormal CK-MB can occur in the absence of an elevated total CK.)
30. Which of the following is the most effective serial sampling time for ruling out AMI using both myoglobin and a cardiac specific marker in an emergency department environment? A. Admission and every hour for the next 3 hours or until positive B. Admission, 2 hours, 4 hours, and 6 hours or until positive C. Admission, 3 hours, 6 hours, and a final sample within 12 hours D. Admission and one sample every 8 hours for 48 hours
C (Since the time between the onset of symptoms and arrival in the emergency department is often speculative, serial measurement of cardiac markers is required in order to rule out AMI. Since myoglobin is the first marker to rise after AMI, if used it should be measured on admission. Since TnI, TnT, and CK-MB are more cardiac specific, at least one should be measured starting at 3 hours postadmission, and again at 6 hours postadmission. If all results are negative to this point, a final assay should be performed 6-12 hours postadmission to conclusively rule out the possibility of AMI and evaluate the short-term risk of AMI.)
23. Which of the following statements regarding total CK is true? A. Levels are unaffected by strenuous exercise B. Levels are unaffected by repeated intramuscular injections C. Highest levels are seen in Duchenne's muscular dystrophy D. The enzyme is highly specific for heart injury
C (Total CK is neither sensitive nor specific for AMI. An infarct can occur without causing an elevated total CK. Exercise and intramuscular injections cause a significant increase in total CK. Crush injuries and muscular dystrophy can increase the total CK up to 50 times the URL)
29. What is the typical time course for plasma TnI or TnT following an AMI? A. Abnormal within 3 hours; peaks within 12 hours; returns to normal in 24 hours B. Abnormal within 4 hours; peaks within 18 hours; returns to normal in 48 hours C. Abnormal within 4 hours; peaks within 24 hours; returns to normal in 1 week D. Abnormal within 6 hours; peaks within 36 hours; returns to normal in 5 days
C (Troponin is a complex of three polypeptides that function as a regulator of actin and tropomyosin. The three subunits are designated TnC, TnI, and TnT. All are present in both cardiac and some skeletal muscles, but cardiac and skeletal isoforms of TnI and TnT can be differentiated by specific antiseras. TnI and TnT cardiac isoforms in plasma will at least double within 4-6 hours after MI, peak within 24 hours and usually remain elevated for 7-10 days. TnT and TnI have the same sensitivity, but TnT is more commonly elevated in renal failure patients. Both are increased slightly in unstable angina (chest pain while at rest) and cardiac ischemia.)
21. SITUATION: A specimen for CK performed on an automated analyzer using an optimized Oliver-Rosalki method gives an error flag indicating substrate depletion. The sample is diluted 1:2 and 1:4 by the serial dilution technique and reassayed. After correcting for the dilution, the results are as follows: 1:2 Dilution = 3,000 IU/L 1:4 Dilution = 3,600 IU/L Dilutions are made a second time and assayed again but give identical results. What is the most likely explanation? A. The serum became contaminated prior to making the 1:4 dilution B. The wrong pipet was used to make one of the dilutions C. An endogenous competitive inhibitor is present in the serum D. An error has been made in calculating the enzyme activity of one of the two dilutions
C (When a competitive inhibitor is present in the serum, a dilution of the sample will cause an increase in the reaction rate by reducing the concentration of the inhibitor. Dilution of serum frequently increases the activity of CK and amylase. The same effect will occur when a smaller volume of serum is used in the assay because less inhibitor will be present in the reaction mixture.)
36. Which of the following laboratory tests is a marker for ischemic heart disease? A. CK-MB isoforms B. Myosin light chain 1 C. Albumin cobalt binding D. Free fatty acid binding protein
C (When heart muscle suffers reversible damage as a result of oxygen deprivation, free radicals are released from the cells and bind to circulating albumin. The albumin is modified at the N-terminus, causing a reduced ability to bind certain metals. This ischemia-modified albumin can be measured by its inability to bind cobalt. An excess of cobalt is incubated with plasma followed by addition of dithiothreitol. The sulfhydryl compound complexes with the free cobalt, forming a colored complex. The absorbance of the reaction mixture is directly proportional to the ischemia-modified albumin concentration. In addition to ischemia-modified albumin, glycogen phosphorylase-BB is a marker for ischemia because it is released from heart muscle during an ischemic episode. Myosin light chains and fatty acid-binding protein are released from necrotic heart tissue in the early stages of AMI.)
43. Select the products formed from the forward reaction of ALT. A. Aspartate and alanine B. Alanine and α-ketoglutarate C. Pyruvate and glutamate D. Glutamine and NAD+
C (because glutamate is a common product for transaminases, pyruvate (a three-carbon ketoacid) and glutamate would be generated from the transamination reaction between alanine and α-ketoglutarate.)
3. Which of the following statements regarding enzymatic reactions is true? A. The enzyme shifts the equilibrium of the reaction to the right B. The enzyme alters the equilibrium constant of the reaction C. The enzyme increases the rate of the reaction D. The enzyme alters the energy difference between reactants and products
C (An enzyme will accelerate the rate of a reaction, reducing the time required to reach equilibrium. The concentration of reactants and products at equilibrium will be the same with or without the enzyme)
14. In which condition is the LD most likely to be within normal limits? A. Hepatic carcinoma B. Pulmonary infarction C. Acute appendicitis D. Crush injury
C (LD is increased slightly to moderately in most causes of liver disease. Smallest elevations are seen in obstructive jaundice and highest in hepatic carcinoma and toxic hepatitis, where levels can reach 10-fold the upper reference limit. LD is also increased in crush injury and muscular dystrophies due to skeletal muscle damage, and in pulmonary infarction owing to embolism formation. Amylase is increased in a majority of persons with acute appendicitis, but LD is not)
1. An international unit (IU) of enzyme activity is the quantity of enzyme that: A. Converts 1 μmol of substrate to product per liter B. Forms 1 mg of product per deciliter C. Converts 1 μmol of substrate to product per minute D. Forms 1 μmol of product per liter
C (The IU is a rate expressed in micromoles per minute. Activity is reported as IUs per liter (IU/L) or mIU/mL. The SI unit for enzyme activity is the katal (1 katal converts 1 mol of substrate to product in 1 second))
40. Which of the following cardiac markers derived from neutrophils predicts an increased risk for myocardial infarction? A. Phospholipase A2 (PLA2) B. Glycogen phosphorylase BB (GPBB) C. Soluble CD40 ligand (sCD40l) D. Myeloperoxidase (MPO)
D (All of the answer choices are markers for acute coronary syndrome and increased risk of AMI. MPO is released from neutrophils and is thought to destabilize the arterial plaque by oxidizing both LDL and HDL and reducing nitric oxide levels in the coronary arteries. Levels in the upper third quartile predict an increased risk of a coronary event even when troponin is normal. GPBB is released from myocytes early in an ischemic episode and becomes abnormal about 2 hours after an AMI. sCD40l is released from activated platelets and indicates an unstable plaque. PLA2 is produced by the arterial wall. It removes a fatty acid from phospholipids and increases the amount of oxidized LDL, leading to foam cell formation. Like hs-CRP, it is a marker for an inflamed plaque.)
22. SITUATION: A physician calls to request a CK on a sample already sent to the laboratory for coagulation studies. The sample is 2-hour-old citrated blood and has been stored at 4°C. The plasma shows very slight hemolysis. What is the best course of action and the reason for it? A. Perform the CK assay on the sample because no interferent is present B. Reject the sample because it is slightly hemolyzed C. Reject the sample because it has been stored too long D. Reject the sample because the citrate will interfere
D (CK activity is lost with excessive storage, the most labile isoenzyme being CK-1. However, CK in serum is stable at room temperature for about 4 hours and up to 1 week at 4°C provided that an optimized method is used. Slight hemolysis does not interfere because CK is absent from RBCs. More significant hemolysis may cause positive interference by contributing ATP, glucose-6-PO4, and adenylate kinase to the serum. Calcium chelators remove magnesium as well as calcium and should not be used.)
37. Which test becomes abnormal in the earliest stage of the acute coronary syndrome? A. Myosin light chain 1 B. CK-MB isoforms C. Myoglobin D. High-sensitivity C-reactive protein
D (The acute coronary syndrome (ACS) refers to the evolution of coronary artery events that lead up to AMI. Coronary artery disease (CAD) begins with formation of a plaque comprised of lipid from dead endothelium that proliferates into the artery lumen. The plaque becomes disrupted and the vessel wall inflamed in the asymptomatic stage of CAD. If platelet activation occurs and results in thrombosis, blood flow becomes significantly reduced, resulting in angina. This signals the transition to more advanced disease in which ischemia to heart muscle occurs and eventually to AMI. Myoglobin and CK-MB isoforms are not increased until the end stage of ACS. High-sensitivity C-reactive protein (hs-CRP) is an ultrasensitive CRP assay that accurately measures CRP below 1 mg/L. CRP is an acute-phase protein increased in inflammation. Levels of CRP between 3.2-10 mg/L signal low-grade inflammation, which occurs in the asymptomatic phase of ACS. Such inflammation occurs when coronary artery plaques become disrupted, and therefore, persons with CAD who have a mildly increased CRP are at high risk of disease progression. Glycogen phosphorylase-BB and albumin cobalt binding are increased by ischemia. Troponins are increased when there is unstable angina and ischemic injury, and indicate an increased risk for AMI.)
33. A patient has a plasma myoglobin of 10 μg/L at admission. Three hours later, the myoglobin is 14 μg/L and the troponin I is 0.02 μg/L (reference range 0-0.03 μg/L). These results are consistent with which condition? A. Skeletal muscle injury B. Acute myocardial infarction C. Unstable angina D. No evidence of myocardial or skeletal muscle injury
D (This person displays very low plasma myoglobin (reference range for females is approximately 17-75 μg/L). The TnI result is also within normal limits. These results are consistent with baseline levels and no evidence of cardiac or skeletal muscle injury. TnI cutpoints for diagnosis of AMI are dependent upon the method, and may be higher than the upper limit of normal. Troponin results above the upper reference limit but below the cutpoint for AMI indicate myocardial injury and increased risk for AMI.)
4. Which statement about enzymes is true? A. An enzyme alters the Gibb's free energy of the reaction B. Enzymes cause a reaction with a positive free energy to occur spontaneously C. An enzyme's natural substrate has the highest Km D. A competitive inhibitor will alter the apparent Km of the reaction
D (Enzymes alter the energy of activation by forming a metastable intermediate, the enzyme substrate complex. Enzymes do not alter the free energy or direction of a reaction. Competitive inhibitors bind to the active site where the enzyme binds substrate and are overcome by increasing the substrate concentration.)
9. Which of the following enzymes is considered most tissue specific? A. Creatine kinase (CK) B. Amylase C. Alkaline phosphatase (ALP) D. Alcohol dehydrogenase (ADH)
D (No enzyme is truly tissue specific and diagnostic accuracy depends upon recognizing changes in plasma levels that characterize different diseases. This includes the mass or activity of enzyme released, its rise, peak, and return to normal, the isoenzyme(s) released, and the concomitant changes of other enzymes. Alanine aminotransferase and alcohol dehydrogenase are primarily increased in necrotic liver disease)
8. The increase in the level of serum enzymes used to detect cholestatic liver disease is caused mainly by: A. Enzyme release from dead cells B. Leakage from cells with altered membrane permeability C. Decreased perfusion of the tissue D. Increased production and secretion by cells
D (The amount of enzyme in the serum can be increased by necrosis, altered permeability, secretion, or synthesis. It is also dependent upon tissue perfusion, enzyme half-life, molecular size, and location of the enzyme within the cell. Most enzymes are liberated by necrosis, but a few, such as ALP and γ-glutamyltransferase, are produced and secreted at a greater rate in obstructive liver disease.)
15. The LD pleural fluid:serum ratio for a transudative fluid is usually: A. 3:1 or higher B. 2:1 C. 1:1 D. 1:2 or less
D (The lactate dehydrogenase activity of body fluids is normally less than serum, and a fluid to serum LD ratio greater than 1:2 is highly suggestive of an exudative process. Elevated lactate dehydrogenase in chest fluid is often caused by lung malignancy, metastatic carcinoma, Hodgkin's disease, and leukemia.)
